Immunological studies correlating immune parameters, including immunophenotype, with outcome in leukemia may assist in the assessment of prognosis and the selection of patients more suited to particular forms of therapy. For example, CALGB has published results correlating outcome of acute lymphoblastic leukemia (ALL) patients with certain leukemic immunophenotypes identified at diagnosis (Czuczman et al., 1999). The expression of CD38 by chronic lymphocytic leukemia (CLL) cells has been reported to predict a poor outcome, possibly identifying such patients for more aggressive therapies (Jelinek et al., 2001; Chevallier et al., 2002). In addition, other detailed immunologic correlative studies, beyond immunophenotyping, are also likely to be helpful in the determining which patients may benefit from immunotherapy-based strategies. Over the past seven years, CALGB has initiated a number of immunotherapy trials with the goal of ultimately investigating the anti-leukemic efficacy of the innate immune system in acute myeloid leukemia (AML) (CALGB 9420, 9621, 9720, and 19808). Recent understanding of the importance of natural killer (NK) cell receptors for the recognition and lysis of leukemic target cells, however, suggests that not all patients are likely to benefit from this immunotherapeutic strategy (Farag et al., 2002a). In this respect, studies directed at identifying patients whose leukemic cells are susceptible to recognition and lysis by autologous NK cells is, therefore, highly relevant. The need for the investigation and correlation of immune parameters with outcome in CALGB leukemia trials has resulted in the conception of this Project. This Project will interact with Leukemia Committee clinical trials and with the Leukemia Correlative Sciences Committee projects. The goal of this project, Immunologic Assessment in Leukemia, will be to utilize flow cytometry and functional immunological assays, including cytotoxicity assays of cloned immune (NK) cells, for correlation of results with outcome of patients treated on CALGB ALL and CLL treatment protocols, and AML patients treated on CALGB immunotherapy protocols.